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Overcoming immune #imprinting with the #COVID19 #LP81 #mRNA #boosters

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By G.M.

 


{Summary}

In summer 2025, the SARS-CoV-2 JN.1 sublineage became dominant with more resistant variants, such as XFG, LP.8.1, and NB.1.8.1. COVID-19 mRNA boosters were therefore updated for the 2025–2026 season to target the LP.8.1 spike.1 Previous boosters, particularly the WA1/2020+BA.5 bivalent booster, were characterised by substantial boosting of the ancestral strain, a phenomenon known as immune imprinting.2,3 We therefore evaluated whether the phylogenetically more distant LP.8.1 mRNA booster would preferentially boost currently circulating strains. Recent data from European and Asian populations have reported the immunogenicity of the LP.8.1 mRNA booster.4,5 Herein, we report the immunogenicity of the LP.8.1 mRNA booster in a US population with a different exposure history and high population immunity. We show that the LP.8.1 mRNA booster induced neutralising antibody (NAb) and binding antibody responses, primarily to the vaccine-matched L.P.8.1 variant and other currently circulating variants and lower responses to the ancestral WA1/2020 strain.

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